The effects of
ellipticine [5,11-dimethyl-6H-pyrido(4,3-b)
carbazole;
NSC 71795] on cell viability, growth, and colony formation were investigated in
suspension (Friend
leukemia and L1210) and adherent [Chinese hamster ovary (CHO)]
tumor cell systems as well as in
mitogen-stimulated human peripheral blood lymphocyte cultures. Cell cycle progression and the terminal point of action of the
drug were monitored by flow cytometry.
Ellipticine was
cytostatic for all cell lines tested, blocking cells in G2 phase following 24 hr constant exposure at concentrations in the range of 1.0 microgram/ml.
A 10 times higher
drug concentration was required to block cells in G2 if the cells were exposed for only 30 min to the
drug followed by 23.5 hr culture in
drug-free medium. Formation of CHO cell colonies was inhibited by 50% following exposure to
ellipticine for 2 hr at 6.0 microgram/ml or for 24 hr at 0.3 microgram/ml. Fifty % cell kill in asynchronously growing Friend
leukemia and L1210 cells was obtained following exposure to
ellipticine for 24 hr at 2.0 microgram/ml and 1.15 microgram/ml, respectively, whereas human peripheral blood lymphocytes required 66 hr exposure to 1.0 microgram/ml to kill 50% of the cells.
Phytohemagglutinin-stimulated lymphocytes were remarkably resistant to the cytotoxic effect of
ellipticine but did display a dose-dependent inhibition of stimulation and accumulation in G2 whether the
drug was added prior to our during active cell proliferation.
Ellipticine, at
cytostatic concentrations, had a marked effect on cellular
RNA content. Friend
leukemia cells, blocked in G2 by the
drug, doubled their
RNA content compared to control cells. L1210 and CHO cells, but not lymphocytes, also increased in
RNA content following
ellipticine treatment.
Drug concentrations which blocked cells in G2 also led in the case of Friend
leukemia and L1210 but not CHO cells to an increase in the proportion of cells with greater than 4C amounts of
DNA.